当归多糖促进5-氟尿嘧啶作用后小鼠应激性红细胞发生

Angelica sinensis polysaccharide promotes stress erythropoiesis in mice caused by 5-FU

目的探讨当归多糖(Angelica sinensis polysaccharide,ASP)拮抗5-氟尿嘧啶(5-fluorouracil,5-FU)对小鼠脾脏应激性红细胞发生的影响及其相关机制。方法选取6~8周龄的C57BL/6J小鼠,雌雄各半,分为对照组、ASP组、5-FU组、ASP+5-FU组。记录建模时期小鼠体质量,血细胞计数仪分析外周血常规;观察脾脏组织切片病理学改变;计算脾指数;台盼蓝染色法计数小鼠股骨骨髓单个核细胞及脾细胞数;分离培养及计数脾脏单个核细胞爆氏红系集落形成单位;流式细胞术检测F4/80+脾巨噬细胞数量;qRT-PCR检测脾脏黏附分子基因Emp,铁转运基因Hmox-1、Trf、Fpn、TrfR以及核内吞基因Tim4、MerTK表达水平。结果ASP部分逆转5-FU致伤小鼠体质量、红细胞数量、血红蛋白含量和红细胞压积、骨髓单个核细胞数量下降;ASP增大脾脏体积、提升脾指数、红髓面积、脾细胞数量,促进脾脏BFU-E形成;ASP拮抗5-FU,维持F4/80+脾巨噬细胞数量,促进Emp、Hmox-1、Trf、Fpn、TrfR、Tim4及MerTK基因表达。结论ASP通过保护脾脏幼红细胞岛中央巨噬细胞数量及功能,促进小鼠脾脏应激性红细胞发生。

Aim To investigate the effects of angelica sinensis polysaccharide(ASP)antagonizing 5-fluorouracil(5-FU)on spleen stress erythropoiesis in mice and its related mechanism.Methods C57BL/6J mice aged 6-8 weeks were randomly divided into control group,ASP group,5-FU group and ASP+5-FU group.The mouse body weight during the modeling period was recorded,and peripheral blood routine and the number of mononuclear cells in the bone marrow of femur were measured.Histopathology of spleen was detected,also the index and cellularity of spleen were analyzed.BFU-E of spleen mononuclear cells was counted.The number of F4/80+splenic macrophages was detected by flow cytometry.The expression levels of adhesion molecule genes Emp,iron transport genes including Hmox-1,Trf,Fpn and TrfR,endocytosis genes including Tim4 and MerTK were detected by qRT-PCR.Results ASP partially reversed the decrease of mice body weight,erythrocytes number,hemoglobin content,hematocrit and the cellularity of bone marrow mononuclear cells induced by 5-FU.ASP increased spleen volume,spleen index,red pulp area,the number of splenocytes,and promoted spleen BFU-E formation.ASP antagonizing 5-FU,maintained the number of F4/80+splenic macrophages,and up-regulated the gene expression of Emp,Hmox-1,Trf,Fpn,TrfR,Tim4 and MerTK.Conclusions ASP promotes stress erythropoiesis in spleen of mice by protecting the number and function of central macrophages of splenic erythroblast islands.